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Completed

NCT Number: NCT03030599

A Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy

This is a double-blind, placebo-controlled, randomized-withdrawal, multicenter study of the efficacy and safety of JZP-258.

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Key information

Conditions

Narcolepsy With Cataplexy Disorders of Excessive Somnolence Dyssomnias Mental Disorders Narcolepsy Nervous System Diseases Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

UZ Antwerpen, Edegem, Belgium

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About this study

Subjects will be transitioned to JZP-258 based on their treatment status at study entry. All subjects will begin JZP-258 treatment at the beginning of this period and continue through Week 12. They will be treated with JZP-258 alone for the final two weeks of this 12-week period. Once the JZP-258 dose has been optimized per the Investigator's judgment, these subjects may enter the 2-week Stable-Dose Period with that dose. Subjects are eligible to enter the Double-Blind Randomized-Withdrawal Period if the dose of JZP-258 remains unchanged during the Stable-Dose Period and, in the judgment of the Investigator, no clinically significant worsening in narcolepsy symptoms or clinically significant adverse events due to JZP-258 treatment have occurred. Subjects will return for a Safety Follow-up visit 2 weeks after the Double-Blind Randomized-Withdrawal Period. Subjects who complete the double-blind treatment period during the Main Study are eligible to enter a 24-week Open-Label Extension. During this period subjects will receive open label JZP-258. Subjects will return for a Safety Follow-up visit 2 weeks after the Open-Label Extension Period.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Male or female subjects between 18 and 70 years of age, inclusive.
  • Have a primary diagnosis of narcolepsy with cataplexy that meets ICSD-3 criteria or DSM-5 criteria, and currently untreated or treated with or without anticataplectics.
  • If applicable, treated with a stimulant or alerting agent at unchanged doses for at least 2 months prior to dosing or not treated with a stimulant or alerting agent.
  • Willing and able to comply with the study design schedule and other requirements.
  • Willing and able to provide written informed consent.

Exclusion criteria

  • Narcolepsy secondary to another medical condition (e.g., CNS injury or lesion)
  • History or presence of any unstable or clinically significant medical condition, behavioral or psychiatric disorder (including active suicidal ideation), or history or presence of another neurological disorder or surgical history that might affect the subject's safety and/or interfere with the conduct of the study in the opinion of the Investigator.
  • Treatment with any central nervous system sedating agents, including but not limited to benzodiazepines, nonbenzodiazepine anxiolytics/ hypnotics/sedatives, neuroleptics, opioids, barbiturates, phenytoin, ethosuximide, or MCT inhibitors, e.g. diclofenac, valproate, ibuprofen, within 2 weeks prior to enrollment (discontinuation for the purpose of study enrollment is permitted only if considered safe by the Investigator and approved by the Medical Monitor).
  • Treatment with an antidepressant for cataplexy, if the withdrawal of the antidepressant during cross-titration with JZP-258 might be unsafe due to prior history of depression.
  • Unsafe for the subject to receive placebo treatment for 2 weeks, in the opinion of the Investigator.

Treatment and study plan

JZP-258

Drug

JZP-258 oral solution 0.5 g/mL, which is equivalent to 0.413 g/mL of oxybate

Other names: Xyrem®

Placebo

Other

Matching placebo solution (aqueous solution containing sodium citrate, malic acid, and sucralose; all ingredients were compendial [United States Pharmacopeia/ National Formulary])

Primary outcomes

  1. Change in Weekly Number of Cataplexy Attacks

    Time frame: Change from baseline (2 weeks of the Stable Dose Period) to the 2 weeks of the Double Blind Randomized Withdrawal Period (DB RWP)

    Participants completed a daily Cataplexy Frequency Diary each night prior to bedtime. Participants were to record the number of cataplexy attacks that they had each day.

Secondary outcomes

  1. Change in the Epworth Sleepiness Scale (ESS) Score

    Time frame: From the end of the Stable Dose Period to the end of the Double Blind Randomized Withdrawal Period

    This is the key secondary endpoint. The Epworth Sleepiness Scale (ESS) was a self-administered questionnaire with 8 questions. Participants were asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. Most participants engaged in those activities at least occasionally, although not necessarily every day. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that participants average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.

  2. Number of Participants With Worsening Patient Global Impression of Change (PGIc) for Narcolepsy Overall

    Time frame: At the end of the Double Blind Randomized Withdrawal Period

    At the end of the Double Blind Randomized Withdrawal Period (DB RWP), participants rated the change in their condition on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse" since the last visit. This endpoint measures the percentage of participants with worsening PGIc scores for narcolepsy overall (defined as scores of Much Worse or Very Much Worse).

  3. Number of Participants With Worsening Clinical Global Impression of Change (CGIc) for Narcolepsy Overall

    Time frame: At the end of the Double Blind Randomized Withdrawal Period

    At the end of the Double Blind Randomized Withdrawal Period, Investigators rated their impression of any change in the severity of the participant's narcolepsy overall condition since the start of the Double Blind Randomized Withdrawal Period on a 7-point scale ranging from 1 = "very much improved" to 7 = "very much worse". This endpoint measures the percentage of participants with worsening CGIc scores for narcolepsy overall, defined as scores of Much Worse or Very Much Worse.

  4. Change in 36-Item Short Form Health Survey Version 2 (SF-36v2) Scores

    Time frame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period

    The SF-36v2 is a multi-purpose, short-form health survey with 36 questions/ items. It yields an 8-scale profile of functional health and well-being scores as well as a psychometrically-based physical and mental overall component summary measures. Two summary scores were derived using the SF-36v2. Physical Component Summary measures dimensions of functional health that are meaningful to respondents, including the impact of health and health-related changes on physical function, pain, and the ability to carry out daily roles. The Mental Component Summary component scale measures the impact of health and health-related changes on well-being, including vitality, social function, and emotional well-being. Participants self-report on items in a summary that have between 2-6 choices per item (e.g. none of the time, some of the time, etc.). Summations of item scores were transformed into a range from 0 to 100; zero= worst HRQL, 100=best HRQL. Higher scores indicate better health status.

  5. Change in 5-level EQ-5D (EQ-5D-5L) Crosswalk Index Score and Visual Analog Scale

    Time frame: At the End of the Stable Dose Period to the End of the Double Blind Randomized Withdrawal Period

    The EQ-5D-5L is a measure of health outcome that includes a descriptive system consisting of 5 dimensions (mobility, self-care, usual activities, pain/ discomfort, and anxiety/ depression). The EQ-5D-5L includes 5 levels of severity for each of the 5 dimensions of the descriptive system (1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems) that reflect increasing levels of difficulty. The 5 digit health states for each dimension are converted into a single value per country (0= equivalent to death, 1= equivalent to best imaginable health and values below 0= health states rated worse than death capped at -1), using the EQ-5D-5L crosswalk index value calculator as recommended by EuroQol group. A visual analogue scale (VAS) used within this scale recorded the participants self-rated health on a VAS and the endpoints resulted in a numeric value set ranging from 0 (= worst imaginable health state) up to 100 (= best imaginable health state).

Sponsors and collaborators

Lead sponsor

Jazz Pharmaceuticals

Industry

Registry information

Official study title

A Double-Blind, Placebo-Controlled, Randomized-Withdrawal, Multicenter Study of the Efficacy and Safety of JZP-258 in Subjects With Narcolepsy With Cataplexy

Important dates

Study start
2017
Primary completion
2019
Study completion
2019
First posted
Jan 25, 2017
Registry last updated
Nov 12, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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